Coag Final

Coag cascade

Virchows Triad

All work together to impact how clotting would happen:

1. changes in the vessel wall

2. changes in the blood composition

3. changes in the blood flow

Role of intact endothelium

-thrombo resistant ( resist blood clotting)

-first to respond to injury by vasoconstriction

How is the Endothelium Thrombo resistant?

1. secretes substances to keep plts from sticking

2. makes thrombomodulin

3. releases t-PA (tissue plasminogen activator)

4. Heparan sulfate

What occurs when endothelium is damaged?

Thrombogenic (clot inducing) by

1. exposing collagen receptors to trigger plt adhesion

2. endothelial cells release TXA2 to activate plts

3. Weibel Palade bodies release vWf (bind plts)

4. release of tissue factor (trigger extrinsic)

5. release of PAI 1, 2, 3, 4 (limit fibrinolysis)

Maturation sequence of plts

1. Megakaryoblast

2. Promegakaryocyte

3. Megakaryocyte

4. plt

Lifespan of plts

7-10 days

Where do plts reside?

1/3 spleen

2/3 in circulation

What are the 4 zones of plts (MOPS)

1. membranous: facilitates granule release

2. organelle: release alpha granules and dense bodies

3. peripheral zone: glycoprotein receptors, phospholipids (pf3)

4. structural: shape change

What receptor on plts binds vWF

GPIb-IX

What receptor on plts binds fibrinogen

GPIIb-IIIa

What do alpha granules contain?

1. platelet factor 4

2. PDGF

3. Beta thromboglobulin

4. coag factors (1, vWF, 5, 8, 11, 13, protein S, plasminogen, PAI-1)

plt factor 4 neautralizes____

heparin

PDGF starts ______repair with fibroblasts

wound

Beta thromboglobulin neautralizes_____

heparin

What do dense bodies contain?

1. ADP and calcium

2. Serotonin

Serotonin is an _____agent

aggregating

Which granules in plts are more numerous?

alpha granules

Which granules in plts play a bigger role?

dense bodies

Describe the process of aggregation (4xA)

1. Activation: collagen exposed

2. Adhesion: vWF binds to exposed endothelium and plts bind to it via GPIb/IX

3. Activation: GPIIb/IIIa on plts is exposed and granules release

4. Aggregation: fibrinogen can then bind and clot

Which CD marker detects GPIb/IX

CD42

Which CD marker detects GPIIb/IIIa

CD41

A stimulating chemical is called an____

agonist

Dense bodies release ____and____

ADP and calcium

What role does ADP play?

binds to plt membrane—→ activates enzymes——> arachidonic acid released

Archidonic acid ——(cyclooxygenase+ thromboxane synthase)——> _________

Thromboxane A2

What does Thromboxane A2 do?

complete or amplify aggregation

What inactivates cyclooxygenase?

aspirin

How would you determine if bleeding is due to plts (primary)?

1. family history

2. Type of bleeding

3. Screening tests

What type of bleeding occurs in primary hemostasis (due to plts)

• epistaxis (nose bleeds)

• mucous membrane

• external skin: bruising, petechiae

What are the screening tests for primary hemostasis?

• plt count

• plt function

List disorders of primary hemostasis (HOME)

1. Hereditary hemorrhagic telangiectasia

2. Osteogensis imperfecta

3. Marfans syndrome

4. Ehlers Danlos Syndrome

• They all lack the right amount or composition of collagen

Thrombocytopenia

low plts

Normal range for plts

150-400

List some disease that have decr plts

1. Myelophthisic

2. Aplastic

3. Myelodysplastic

4. Acute Leukemia

5. Megaloblastic anemia

6. Chemotherapy

What are immune mechanism that destroy plts?

1. Chronic ITP (immune thrombocytopenic purpura)

2. Acute ITP

3. HIT (heparin induced thrombocytopenia)

Acute ITP

.

Age range:

Gender:

Treatment:

Age range: kids post viral

Gender: any

Treatment: self limiting

Chronic ITP

.

Age range:

Gender:

Treatment:

Age range: child bearing age

Gender: females

Treatment: steroids, splenectomy, doesn’t resolve

HIT antibodies made against:

-plt- factor 4 complex

-Can cause bleeding or clotting

• bleeding: destroys plts

• clots: activates plts

What are non-immune mechanism that destroy plts?

1. TTP (Thrombotic thrombocytopenic purpura)

2. HUS (Hemolytic Uremic Syndrome )

3. DIC (Disseminated Intravascular Coagulation)

TTP

Trigger:

Coag results:

Trigger: ADAMS 13

Coag results:

• large vWF

• PT normal

• PTT normal

• D-dimer (-)

HUS

Trigger:

Coag results:

Trigger: Ecoli O157 ( endotoxin exposes sub endothelial in kidneys)

Coag results:

• PT normal

• PTT normal

• (it is not a systemic problem therefore normal)

DIC

Trigger:

Coag results:

Trigger: OB, Sepsis, Leukemia, Burns, Trauma

Coag results:

• all factors consumed

• PT long

• PTT long

• D-dimers (+)

Secondary fibrinolysis occurs in ___ where clots are being lysed

DIC

Which disorder corrects itself if given enough ADP?

Aspirin induced

Test for plt function

1. Bleeding time (obsolete)

2. Plt function analyzer (PFA-100)

3. Verify Now test for P2Y12 (ADP) inhibition

   • Plavix

Plavix

Antiplatelet drug that blocks P2Y12 ADP receptor site on plts

PFA-100 results for Aspirin

EPI: abnormal

ADP: norm

PFA-100 results for vWD

EPI: abnormal

ADP: abnormal

PFA-100 results for Bernard Soulier

EPI: abnormal

ADP: abnormal

PFA-100 results for Glanzmans

EPI: abnormal

ADP: abnormal

Defect of Glanzmans

GP IIB/IIIA

Defect of Bernard Soulier Syndrome

GP IB/IX

Defect of vWD

vWF

Defect of storage pool disorders (includes aspirin)

Lack of granule release

Plt Agg results for Bernard Soulier

• ADP: norm

• Collagen: norm

• Epinephrine: norm

• Ristocetin: abnormal

• Ristocetein +NL plasma: abnormal

Plt Agg results for vWD

• ADP: norm

• Collagen: norm

• Epinephrine: norm

• Ristocetin: abnormal

• Ristocetein +NL plasma: norm

Plt Agg results for Glanzman’s

• ADP: abnormal

• Collagen: abnormal

• Epinephrine: abnormal

• Ristocetin: norm

• Ristocetein +NL plasma: norm

Plt Agg results for storage pool disorders

• ADP: starts then disintegrates

• Collagen: starts then disintegrates

• Epinephrine: starts then disintegrates

• Ristocetin: norm

• Ristocetein +NL plasma: norm

• Archidonic acid: if still abnormal then aspirin

Extrinsic factors

7 (common-10, 5, 2, 1)

Extrinsic measured by

PT

Instrinsic

12, 11, 9, 8, (common 10, 5, 2, 1)

Intrinsic measured by

PTT

Common pathway

10, 5, 2, 1

Common pathway measured by

PT and PTT

What is another name for Factor I

Fibrinogen

What is another name for Factor II

Prothrombin

Contact factors

12, 11, Prekalikrein, HMWK

Vit K dependent factors

2, 7, 9, 10

Fibrinogen group (cofactors)

1 (fibrinogen), 5, 8, 13

What is used to preserve factors 5, 8, 13

cryo-pcpt

What role does thrombin play in plts

trigger for plt activation

Thrombin converts ___to___

fibronogen to fibrin

What role does thrombin play in instrinsic

Amplifies Factor 5, 8, 11, 12

What does thrombin do to factor 13

causes cross linking of fibrin

Thrombin binds to thrombomodulin and causses protein c/s to

activate shut-off mechanism

Endothelial cells bind to _____ to limit action of thrombin

thrombomodulin

What is thrombomodulin?

endothelial cell membrane glycoprotein

Thrombin makes endothelial cells release___

vWF and t-PA

TAFI suppresses___

fibrinolysis

Process of Fibrinogen to fibrin

1. Thrombin cleaves fibrinopepetide A and B

2. Fibrin monomer is formed

3. Fibrin monomer is polymerized

4. F-13 plus Ca creates cross-linked fibrin

What are some bleeding symptoms of secondary hemostasis (factors)

• deep tissue bleeding

• blood in joints

• delayed bleed

• NO petechiae

Hemophilia

Def in clotting proteins

vWD inheritance

Auto Dom

Factor 8 or 9 def inheritance

x-linked recessive

(all other disorders will be recessive)

vWF binds to plt GP____and promotes adhesion to subendothelial collagen

receptors

Why would vWD affect secoondary hemostaisis, specifically factor 8

vWF complexes 1:1 with F-8 to protect and extend its half life

• without vWF F-8 may be subpar and PTT may be slightly long

Type O has the ___vWF

least

Type AB has the ____vWF

most

vWD
PT, PTT, and plt count are___

norm

vWD testing includes

1. vWF antigen

2. vWF activity

3. vWF multimer analysis

4. ADAMS 13 activity

Treatment for vWD

• nosespray (DDADP)

• cryo-pcpt

Hemophilia A def

F-8

Hemophilia B (Christmas) def

F-9

Treatment for Hemophilia

Recombinant F-8, or F-9 concentrate

Some people develop inhibitors called

F-8 or F-9 autoantibodies

Recessive bleeding disorders include all factors except

F-8 and F-9

Recessive bleeding disorders will show what symptoms?

usually none

Hemophilia C def

F-11

Parahemophilia def

F-5